There are various classifications of pain, but in terms of the duration or nature, they may be classified into acute pain which plays a role as a biological alert system and chronic pain in which a duration taken for curing the diseases is exceeded usually but complaints of pain continue. According to the causes, pain can be classified into three main types, that is, nociceptive pain, neuropathic pain, and psychogenic pain. Neuropathic pain refers to intractable chronic pain which occurs as a result of dysfunction of the peripheral or central nervous system. Typical examples of neuropathic pain include pain associated with diabetic neuropathy, postherpetic neuralgia, low back pain and leg pain, trigeminal neuralgia, cancer pain, post-operative or post-traumatic prolonged pain, pain induced by spinal cord injury, thalamic pain, multiple sclerosis-derived pain, a complex regional pain syndrome (CRPS), phantom limb pain, HIV-related neuropathic pain, and the like. There are many unclear points about the onset mechanism of the disease, but believed to be induced by persistent abnormal firing of sensory nerves or the like. Typical examples of neuropathic pain include allodynia, hyperalgesia, hyperesthesia, and the like. These symptoms exhibit characteristic pain which is expressed by “burning”, “pins and needles”, “electric shock-like”, or the like.
It is known that non-steroidal anti-inflammatory analgesics which are effective for common nociceptive pain are ineffective for neuropathic pain, and even narcotic analgesics such as morphine and the like do not work well for neuropathic pain (Non-Patent Document 1). As a treatment method for neuropathic pain, neurosurgical treatments such as nerve block, electrical stimulation of spinal epidural, and the like, an antidepressant (Non-Patent Document 2), an antiepileptic (Non-Patent Document 3), and the like have been used, but a safe and effective treatment method has not been established. In recent years, new drugs such as pregabalin which is a ligand for an α2δ subunit of a voltage-dependent calcium channel have been launched commercially, but their efficacy rates are not so high and there are problems in side effects such as sleepiness, dizziness, and the like. Since a safe and effective treatment method for neuropathic pain has not been still established, there is a strong demand for development of a superior therapeutic agent having fewer side effects with sufficient efficacy.
Fibromyalgia has a core symptom of unbearable chronic pain throughout the whole body, and is a chronic pain disease accompanied by a variety of associated symptoms such as insomnia, systemic fatigue, depressive symptoms, and the like. The symptoms of fibromyalgia are very diverse. The pain symptoms of fibromyalgia are characterized by being accompanied by chronic pain in deep tissues such as muscle tissues, and pain during finger pressure massage. Further, fibromyalgia is often associated with allodynia such as touch allodynia and cold allodynia, or thermal hyperalgesia. Further, as compared with patients with other pain diseases (neuropathic pain, rheumatoid arthritis, osteoarthritis, acute pain after operation, and the like), patients with fibromyalgia have higher rates of being associated with accompanying symptoms including affective disorders such as depression, anxiety, and the like, feeling of fatigue, sleep disorders, irritable bowel syndrome, and the like. For other pain diseases, organic disorder or functional disorder which causes pain are clear to certain degrees, whereas for the patients with fibromyalgia, the causes accounting for pain are not clear. In accordance with the American College of Rheumatology, diagnostic criteria for fibromyalgia is defined as history of widespread pain lasting for at least three months, and pain being present in at least 11 of 18 tender point sites in the whole body (ligaments, tendon, muscles, and the like in contact with the bones) (Non-Patent Document 4). These diagnostic criteria are clearly different from those of other pain diseases. That is, fibromyalgia is a chronic disease which is independently present and clearly different from other pain diseases from the viewpoints of symptoms, causes of pain, diagnostic criteria, and the like.
In recent years, agents including pregabalin (Non-Patent Document 5), duloxetine which is an SNRI (serotonin- and noradrenaline-reuptake inhibitor) (Non-Patent Document 6), pramipexole which is a dopamine agonist (Non-Patent Document 7), and the like have been reported to statistically significantly reduce the pain symptom scores of patients with fibromyalgia, as compared with a placebo group, but the effects of these agents are limited. A safe and effective treatment method for fibromyalgia has yet to be established, and therefore, there is a strong demand for development of a superior therapeutic agent having fewer side effects with sufficient efficacy.
Glucocorticoid is a hormone which causes metabolic disorders such as hyperglycemia, insulin resistance, obesity, hyperlipidemia, hypertension and the like, and is not only produced from adrenal glands but also converted from the inactive form into the active form at the tissue level, and acts via its receptor.
11β-Hydroxysteroid dehydrogenase (11β-HSD) is an enzyme which catalyzes this conversion and the presence of two subtypes thereof is known. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme which converts the inactive form into the active form and highly expressed in the liver, and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is an enzyme which converts the active form into the inactive form and highly expressed in the kidney. 11β-HSD1 has a wide range of substrate specificity (Non-Patent Document 8), but the relation thereof with glucocorticoid is most well-known. Since it has been reported, for example, that an 11β-HSD1 knockout mouse exhibits improved glucose tolerance, lowered blood triglyceride, and increased HDL-cholesterol (Non-Patent Document 9) and a non-selective 11β-HSD inhibitor, carbenoxolone, improves the lowering of insulin secretion in mouse pancreatic β-cell caused by the addition of inactive-form glucocorticoid (Non-Patent Document 10), it is expected that an 11β-HSD1 selective inhibitor inhibits the conversion into active-form glucocorticoid, and thus inhibits the glucocorticoid action in the tissues, and as a result, metabolic abnormalities such as hyperglycemia, insulin resistance, obesity, hyperlipidemia, hypertension, and the like induced by glucocorticoid, are cured (Patent Document 1).
11β-HSD1 is also expressed in the central nervous system such as the brain and the spinal cord (Non-Patent Documents 11 and 12). Since an action of improving language memory by administering a nonselective 11β-HSD inhibitor to a patient with type II diabetes (Non-Patent Document 12), and an action of ameliorating cognition disorders in aged 11β-HSD1 knockout mice (Non-Patent Document 13), and the like have been reported, it is expected that the 11β-HSD1-selective inhibitor inhibits the action of glucocorticoid in the brain through the inhibition of conversion into an active-form glucocorticoid, and as a result, cognition disorders induced by glucocorticoid is cured (Patent Document 1). The 11β-HSD1 inhibitor is also expected to have an effect to ameliorate, in addition to dementia, diseases in the central nervous system, such as schizophrenia, depression, anxiety, post-traumatic stress disorder (PTSD), attention deficit/hyperactivity disorder (AD/HD), panic disorder, somnipathy, and the like, which are greatly related to stress and in which an HPA axis disorder, an increase in cortisol in the blood plasma, or the like is recognized.
As for other diseases in which 11β-HSD1 is involved, osteoporosis and glaucoma are known, and the ameliorating effects by the 11β-HSD1 inhibitor on these diseases are expected.
While the involvement of 11β-HSD1 is known in a number of these diseases, the involvement of 11β-HSD1 in pain has not been clearly known, and in addition, the therapeutic effect of the 11β-HSD1 inhibitor for pain has been unexplained thus far.
As the 11β-HSD1 inhibitor, for example, there are reports of Patent Documents 1 to 11.
In Patent Document 1, it is described that a triazole compound represented by the following general formula (A) has an 11β-HSD1 inhibitory action and is useful for the treatment of diseases such as diabetes, hyperglycemia, insulin resistance, obesity, hyperlipidemia, hypertension, osteoporosis, glaucoma, dementia, schizophrenia, depression, and the like. However, there is no description of usefulness for the treatment of pain.

(Refer to this publication for the symbols in the formula.)
In Patent Document 2, it is described that a triazole compound represented by the following general formula (B) has an 11β-HSD1 inhibitory action and is useful for the treatment of diseases such as diabetes, hyperglycemia, obesity, insulin resistance, dyslipidemia, hyperlipidemia, hypertension, a metabolic syndrome, and the like. However, there is no description of usefulness for the treatment of pain.

(Refer to this publication for the symbols in the formula)
In Patent Documents 3 and 4, it is described that a triazole compound represented by the following general formula (C) has an 11β-HSD1 inhibitory action and is useful for the treatment of diseases such as diabetes, hyperglycemia, hypertension, obesity, insulin resistance, dyslipidemia, hyperlipidemia, hypertension, an X syndrome, and the like. However, there is no description of usefulness for the treatment of pain.

(Refer to this publication for the symbols in the formula.)
In Patent Document 5, it is described that a triazole compound represented by the following general formula (D) has an 11β-HSD1 inhibitory action and is useful for the treatment of diseases such as diabetes, obesity, and a metabolic syndrome. However, there is no description of usefulness for the treatment of pain.

(Z in the formula represents —(CH(R14))p-, —(CH(R14))p-N(R16)—(CH(R15))q-, or
Refer to this publication for other symbols.)
In Patent Document 6, it is described that a triazole compound represented by the following general formula (E) has an 11β-HSD1 inhibitory action and is useful for the treatment of diseases such as diabetes, hyperglycemia, insulin resistance, obesity, hyperlipidemia, hypertension, osteoporosis, glaucoma, lowering of cognitive function, and the like. However, there is no description of usefulness for the treatment of pain.

(Refer to this publication for other symbols in the formula.)
In Patent Document 7, it is described that a triazole compound represented by the following general formula (F) has an 11β-HSD1 inhibitory action and is useful for the treatment of diseases such as diabetes, hyperglycemia, insulin resistance, obesity, hyperlipidemia, hypertension, osteoporosis, glaucoma, lowering of cognitive function, and the like. However, there is no description of usefulness for the treatment of pain.

(In the formula, R1 represents a heterocyclic group or —N(R0)—R4, and A and B represent lower alkyl, or a cycloalkyl ring formed by the combination with carbon atoms to which these are bonded. Refer to this publication for other symbols.)
In Patent Document 8, it is described that a compound represented by the following general formula (G) has an 11β-HSD1 inhibitory action and is useful for the treatment of diabetes, metabolic syndrome, insulin resistance, obesity, glaucoma, hyperglycemia, hyperinsulinemia, osteoporosis, tuberculosis, atherosclerosis, dementia, depression, virus diseases, inflammatory disease, and diseases in which the liver is a target organ. Further, there is a description of pain for lots of diseases exemplified as an inflammatory disease, but there is no description of neuropathic pain.

(Refer to this publication for other symbols in the formula.)
In Patent Document 9, it is described that a compound represented by the following general formula (H) has an 11β-HSD1 inhibitory action and is useful for the treatment of diabetes, metabolic syndrome, insulin resistance, obesity, glaucoma, hyperglycemia, hyperinsulinemia, osteoporosis, atherosclerosis, dementia, depression, virus disease, inflammatory disease, and diseases in which the liver is a target organ. Further, there is a description of pain for lots of diseases exemplified as an inflammatory disease, but there is no description of neuropathic pain.

(Refer to this publication for other symbols in the formula.)
In Patent Document 10, it is described that a compound represented by the following general formula (J) has an 11β-HSD1 inhibitory action and is useful for the treatment of diabetes, metabolic syndrome, insulin resistance, obesity, glaucoma, hyperglycemia, hyperinsulinemia, osteoporosis, atherosclerosis dementia, depression, virus disease, inflammatory disease, and diseases in which the liver is a target organ. Further, there is a description of pain for lots of diseases exemplified as an inflammatory disease, but there is no description of neuropathic pain.

(Refer to this publication for other symbols in the formula.)
In Patent Document 11 which has been published after the priority date of the present application, it is described that an 11β-HSD1 inhibitor such as a compound represented by the following general formula (K) and the like is useful for the treatment of inflammation, chronic inflammation, pain, rheumatoid arthritis (RA), or osteoarthritis (OA), and as specific examples of the pain, pain associated with neuropathic pain and fibromyalgia, and the like are described. However, in Patent Document 11, a test method for neuropathic pain is described, but there is no disclosure of any test results for neuropathic pain and pain accompanied by fibromyalgia is described only in one line.

(Refer to this publication for other symbols in the formula.)